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. 2017 Nov 15;17(1):198.
doi: 10.1186/s12883-017-0978-z.

Parkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels

Laura Ibanez  1   2 , Umber Dube  1   2   3 , Benjamin Saef  1   2 , John Budde  1   2 , Kathleen Black  1   2 , Alexandra Medvedeva  1   2 , Jorge L Del-Aguila  1   2 , Albert A Davis  4 , Joel S Perlmutter  4 , Oscar Harari  1   2 , Bruno A Benitez  5 , Carlos Cruchaga  6   7
Affiliations

Parkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels

Laura Ibanez et al. BMC Neurol. .

Abstract

Background: The genetic architecture of Parkinson's Disease (PD) is complex and not completely understood. Multiple genetic studies to date have identified multiple causal genes and risk loci. Nevertheless, most of the expected genetic heritability remains unexplained. Polygenic risk scores (PRS) may provide greater statistical power and inform about the genetic architecture of multiple phenotypes. The aim of this study was to test the association between PRS and PD risk, age at onset and cerebrospinal fluid (CSF) biomarkers (α-synuclein, Aβ1-42, t-tau and p-tau).

Methods: The weighted PRS was created using the genome-wide loci from Nalls et al., 2014 PD GWAs meta-analysis. The PRS was tested for association with PD status, age at onset and CSF biomarker levels in 829 cases and 432 controls of European ancestry.

Results: The PRS was associated with PD status (p = 5.83×10-08) and age at onset (p = 5.70×10-07). The CSF t-tau levels showed a nominal association with the PRS (p = 0.02). However, CSF α-synuclein, amyloid beta and phosphorylated tau were not found to be associated with the PRS.

Conclusion: Our study suggests that there is an overlap in the genetic architecture of PD risk and onset, although the different loci present different weights for those phenotypes. In our dataset we found a marginal association of the PRS with CSF t-tau but not with α-synuclein CSF levels, suggesting that the genetic architecture for the CSF biomarker levels is different from that of PD risk.

Keywords: Age at onset; Biomarkers; Genetics; Parkinson disease; Polygenic risk score.

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Conflict of interest statement

Ethics approval and consent to participate

Written informed consent was obtained from all participants prior to their enrolment. This study was approved by the Washington University in Saint Louis Institutional Review Board and the Human Research Protection Office (approval number: 201107095).

Consent for publication

Not applicable – this manuscript does not contain any individual person’s data.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Genetic Risk Score distribution between cases and controls. a PRS distribution by PD status. The line represents the controls and the dotted line represents the PD cases. b PRS box plots by PD status. Case contol status is indicated in the x axis
Fig. 2
Fig. 2
Kaplan-Meier Survival and Cumulative Hazards curves for Age at Onset for PD-PRS by Tertiles. A-1st Tertile (black line), B-2nd Tertile (red line), C-3rd Tertile (green line)
See this image and copyright information in PMC

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